• Charge from Dr. McClellan to OWG/Therapeutics (8-03)
– “…[assess] real or perceived barriers to development of
new or enhanced therapeutics”
– “Make recommendations… on…ways to encourage
development of new or enhanced therapeutics”
• Growing public health problem
• Advancing science
• Multiple new drugs in development; anticipated explosion in
development programs in coming years
• Multiple novel mechanistic approaches
• FDA’s role in assuring that safe and effective drugs are
efficiently and effectively brought forward through
development to marketing for use in the treatment of human
disease

Endocrinologic and metabolic Drugs Advisory Committee
September 8, 2004 10
Issues-2 (con’t)
• Duration
– One year of controlled efficacy
– Safety at one year
– Questionable utility of additional year if no safety
concerns after 1st year
– (Approach to assessing need for additional time or patients
not addressed)
• Controls/Combination studies
– (Efficacy criteria not addressed)

• Endpoints
– Define obesity prevention, weight maintenance, prevention of weight regain*
• Are these distinct clinical effects?
• Are these distinct pharmacological effects?
• Are studies needed to document efficacy and safety in each?
– Include requirements for approval of treatment or prevention of drug-induced
obesity*
• Data on risks for and associated with drug-induced obesity, by drug
• Issues of interactions impacting safety and efficacy
• Criteria for efficacy
– Include a section on treatment of obesity in pediatric patients*

Endocrinologic and metabolic Drugs Advisory Committee
September 8, 2004 16
Summary/Discussion-3
– Reduce the number of patients in phase 3 study from 1500 examined
over one year to 500 – 1000, or even fewer*
• Rationale based on magnitude/nature of efficacy?
• Rationale based on size of target population?
• Rationale based on expectations regarding safety?
– Eliminate the second year of open-label study*
• Rationale based on nature of drug “toxicities”: acute vs. cumulative?